Ipilimumab: Let's not get ahead of ourselves

I read an interesting article today entitled "Ipilimumab for Advanced Melanoma: Let’s Not Throw Caution to the Winds." It's a bit technical, but it makes some good if obvious points.

First, there's only one Phase III trial showing benefits for using ipilimumab in patents with metastatic melanoma, so it's still possible that later trials will show less benefit, particularly in light of that first trial's unconventional design. (The control group was given an experimental vaccine, so if somehow that vaccine actually had a negative effect on survival, that could exaggerate the beneficial effects of ipi.) The authors provide the example of a drug called tremelimumab that (like ipi) targets CLTA-4 and showed some early promise but subsequently failed to show a significiant advantage in Phase III testing. Ipilimumab has more evidence backing its efficacy than tremelimumab ever did, but it is still very much an experimental treatment and later trials may have less positive results.

The other thing is that the side effects of ipilimumab can be very serious. In general, ipi isn't as toxic as chemotherapy, but it can still have side effects like colitis, hypophysitis, hepatitis, and a variety of other autoimmune conditions. In some patients (~1-5%) these side effects can be fatal. I've dealt with some moderate side effects myself, and there's a very real cost associated with that.

Despite lingering questions about its efficacy, ipilimumab still represents a tremendous advance. When I was first diagnosed with melanoma on March 29 of last year, no drug had ever showed an overall survival advantage in a Phase III study for patients with metastatic melanoma. That changed less than a month before my melanoma recurred when the initial paper showing the benefits of ipilimumab on June 5. I really can't get over how lucky I am to live when I do. It's awesome to be part of a trial that (hopefully) will provide more evidence for the efficacy of this drug.

I picked up one piece of information from the article that was pretty exciting to me. Apparently the drug seems to have more success in patients who have significant side effects. I've suspected that this is the case all along, and I'm glad that there's actually evidence to support that conclusion. It definitely makes sense. The drug's only direct effect (as far as I know) is to stimulate the immune system, so the cancer fighting effects and any side effects are going to be a function of how effectively it does that. Consequently, the extent of ipilimumab's side effects are a proxy for how much of an effect the ipi will have on the patient's cancer. I already knew that my side effects meant I'm on the drug rather than the placebo; it's good to know that they also mean the drug is working.